The majority of patients who succumb to cirrhosis die due to complications of increased portal venous pressure, such as variceal hemorrhage, ascites, hepatic encephalopathy, hepatopulmonary syndrome, or hepatorenal syndrome (1; 2). The hepatic vein pressure gradient (HVPG), an indirect measure of portal pressure (3), is a prognostic indicator for long term survival in cirrhosis (1; 2). Furthermore, the HVPG can reflect progression of disease in the pre-cirrhotic stage. There is an association between the severity of the hepatic inflammation and fibrosis and the HVPG even before cirrhosis develops (4). In addition, HVPG predicts the response to hepatitis C treatment among patients with cirrhosis (5).
One of the most frequent severe complications of portal hypertension is hemorrhage from gastroesophageal varices (GEV), which is a significant cause of death in patients with cirrhosis. Reduction of the HVPG below 12 mm Hg (normal is 0-5 mm Hg), either through spontaneous reversion after the insult is resolved or with medical, radiological, or surgical interventions, effectively prevents recurrent bleeding (3; 6; 7; 8). Currently, there is no established non-invasive test to predict the portal pressure among patients who are treated medically, and thus, there is no way to predict either the response to standard of care (SOC) or the complications of portal hypertension (including potentially lethal esophageal bleeding) other than performing screening esophagogastroduodenoscopy (EGD) with the added costs and morbidity of the procedure. Although transient elastography has a very good predictive value for clinically-significant portal hypertension, there are some limitations of this technique in patients with chronic liver diseases and with obesity (9).
The ability to predict portal pressure with a simple blood test would revolutionize clinical management of patients with chronic liver diseases, as well as aid in the design and performance of clinical research into the complications of cirrhosis (1; 2). Given that liver inflammation due to liver injury and/or bacterial translocation occurs in liver cirrhosis with portal hypertension (10; 11; 12; 13; 14; 15), it would be desirable to develop a non-invasive test to predict the presence of severe portal hypertension at levels associated with the presence of variceal bleeding (2), as well as to exclude clinically significant esophageal varices so as to avoid and/or prevent the cirrhosis patients from undergoing unnecessary EGD screening.